APPLICANT'S ABSTRACT: Most of the studies examining the deleterious effects of chronic alcohol consumption have primarily been done on males. Based upon these observations, our general understanding regarding the physiological effects of alcoholism has significantly increased. However, recent studies have indicated that females may not respond in the same manner as their male counterparts and may, in fact, be more susceptible to alcohol's deleterious effects. In this regard, while hypoglycemia is recognized as a critical problem for individuals who are chronic alcoholics with poor dietary habits, no studies, to date, have specifically examined gender differences following chronic alcohol consumption. While gender related differences have been observed in the location and quantity of hepatic alcohol dehydrogenase, its impact in the resistance to ethanol-induced hypoglycemia remains unknown. As such, these studies will examine the effects of chronic alcohol consumption upon hepatic gluconeogenic capacity following acute ethanol ingestion in female and male animals. The overall goal is to elucidate for the first time, the pathophysiology behind the gender specific alterations in biochemical and molecular mechanisms associated with the decline in hepatic gluconeogenesis. Investigating the mechanism(s) and factor(s) involved in the attenuated capacity of the liver specific to males and females, may unveil gender related differences in the pathology of ethanol-induced hypoglycemia. Thus, the ability to identify gender susceptibility towards a hypoglycemic event may help to prevent subsequent neuroglycopenia, tissue damage and ultimately death.